Financial strain, stressful social environment, and FKBP5 associate with depressive symptoms in African Americans living in Tallahassee, Florida

The World Health Organization estimates that almost 300 million people suffer from depression worldwide. Depression is the most common mental health disorder and shows racial disparities in disease prevalence, age of onset, severity of symptoms, frequency of diagnosis, and treatment utilization across the United States. Since depression has both social and genetic risk factors, we propose a conceptual model wherein social stressors are primary risk factors for depression, but genetic variants increase or decrease individual susceptibility to the effects of the social stressors. Our research strategy incorporates both social and genetic data to investigate variation in symptoms of depression (CES-D scores). We collected data on financial strain (difficulty paying bills) and personal social networks (a model of an individual’s social environment), and we genotyped genetic variants in five genes involved in stress reactivity (HTR1a, BDNF, GNB3, SLC6A4, and FKBP5) in 135 African Americans residing in Tallahassee, Florida. We found that high financial strain and a high percentage of people in one’s social network who are a source of stress or worry were significantly associated with higher CES-D scores and explained more variation in CES-D scores than did genetic factors. Only one genetic variant (rs1360780 in FKBP5) was significantly associated with CES-D scores and only when the social stressors were included in the model. Interestingly, the effect of FKPB5 appeared to be strongest in individuals with high financial strain such that participants with a T allele at rs1360780 in FKBP5 and high financial strain had the highest mean CES-D scores in our study population. These results suggest that material disadvantage and a stressful social environment increases the risk of depression, but that individual-level genetic variation may increase susceptibility to the adverse health consequences of social stressors.

世界卫生组织（World Health Organization）估计，全球范围内近3亿人罹患抑郁症。抑郁症是最为常见的精神健康障碍（mental health disorder），在美国境内，其患病率、发病年龄、症状严重程度、诊断频率与治疗使用情况均存在种族差异。鉴于抑郁症同时存在社会与遗传风险因素，我们提出一项概念模型：社会应激源为抑郁症的主要风险因素，而遗传变异可增强或减弱个体对社会应激源影响的易感性。本研究策略整合社会与遗传数据，旨在探究抑郁症症状（以流行病学研究中心抑郁量表（Center for Epidemiologic Studies Depression Scale，CES-D）评分表征）的个体差异。我们收集了经济压力（支付账单困难）与个人社交网络（反映个体社会环境）相关数据，并对佛罗里达州塔拉哈西市135名非裔美国人的5个参与应激反应通路的基因（HTR1a、BDNF、GNB3、SLC6A4及FKBP5）的遗传变异开展基因分型。研究结果显示，较高的经济压力以及社交网络中带来压力或困扰的人群占比越高，均与更高的CES-D评分显著相关，且二者对CES-D评分变异的解释度高于遗传因素。仅FKBP5基因的rs1360780这一个遗传变异位点与CES-D评分存在显著关联，且该关联仅在模型纳入社会应激因素时成立。值得注意的是，FKBP5的效应在经济压力较高的个体中最为显著：携带FKBP5基因rs1360780位点T等位基因且经济压力较高的参与者，在本研究人群中拥有最高的平均CES-D评分。上述结果表明，物质层面的劣势与充满压力的社会环境会提升抑郁症发病风险，而个体层面的遗传变异可能会增强个体对社会应激源所引发的不良健康后果的易感性。